The specific aims of the UW TTURC's Developmental Research Core are to: (1) encourage high quality, innovative tobacco control research; (2) encourage investigators who have not previously worked in the tobacco control realm to engage in transdisciplinary collaborations, and (3) amplify the transdisciplinary research activities of the UW TTURC by expanding research opportunities in the four core studies. Mechanisms are presented for actively soliciting and evaluating developmental research applications from a wide variety of sources and disciplines. For the first year, two developmental research studies are proposed that explore themes of tobacco dependence mechanisms, outcomes and treatment mediators highly relevant to the main research proposals. One study uses emerging affective neuroscience methodologies (instructed fear conditioning, fear-potentiated startle assessments) and biological measures to assess potential mediators of response to bupropion. This study has the potential to reveal treatment outcome predictors including mechanisms not available to self-report. The second study seeks to investigate the population of smokers that would be excluded from both classic randomized clinical trials and effectiveness trials: smokers with significant medical or psychiatric comorbidity (including alcohol and/or other drug dependence). Three hundred such individuals will be recruited for a placebo-controlled treatment study that will assess the treatment success in this underserved population. This study will not only provide important estimates of treatment outcomes in an often-overlooked and under-served population, but will also provide novel information on predictors and mediators of treatment response that may be compared with those found in highly motivated volunteers and primary care patients who smoke.